Kardiovaskularne bolesti predstavljaju najveći uzrok smrtnosti ljudske populacije, a njihova glavna i osnovna patološka komponenta je ateroskleroza. Proliferacija ili deoba glatkih mišićnih ćelija krvnog suda (VSMC) ključni je događaj u nastanku raznih vaskularnih oboljenja, uključujući aterosklerozu i hipertenziju. U procesu diferencijacije i abnormalne deobe VSMC povezanih sa hipertenzijom i aterosklerozom uključen je i trombin. Stimulisanje VSMC trombinom dovodi do aktivacije ekstracelularnim signalima regulisanih kinaza 1 i 2 (ERK1/2), preko transaktivacije receptora za epidermalni faktor rasta (EGFR). U ranijim studijama Isenović i saradnici potvrdili su na osnovu inhibicije ERK1/2 od strane PD9805 inhibitora, učešće ERK1/2 u regulaciji proliferacije VSMC izazvanoj trombinom. U nastavku, faktor rasta sličan epidermalnom faktoru rasta koji vezuje heparin (HB-EGF), protein kinaza C delta (PKCδ) i matriksne metaloproteinaze (MMP), nađene su u VSMC i pokazano je da je i njihova aktivnost ardiovascular disease is the largest single cause of mortality and its major underlying pathology is atherosclerosis. The proliferation of vascular smooth muscle cells (VSMC) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. Thrombin is involved in the differentiation and abnormal proliferation of VSMC associated with atherosclerosis and hypertension. Thrombin stimulation results in extracellular signal-regulated kinase (ERK 1/2) activation through transactivation of the epidermal growth factor receptor (EGFR). Based on the studies in which PD98059 used to inhibit ERK1/2, we have shown previously that ERK1/2 was involved in the regulation by thrombin of VSMC’s proliferation. In addition, heparin-binding EGF-like growth factor (HB-EGF) and matrix metalloproteinases (MMPs) have also been detected in VSMC and shown to be regulated by thrombin. ADAMs (A Disintegrin And Metalloproteinase) are transmembrane metalloproteinases, belonging